title: Dissociation and dispersion of claudin-3 from the tight junction could be one of the most sensitive indicators of reflux esophagitis in a rat model of the disease.
abstract: BACKGROUND
  The aim of this study was to characterize pathological lesions of the esophageal epithelial tight junction (TJ) complex in a rat reflux esophagitis (RE) model in a search for a reliable diagnostic indicator.
  
  
  METHODS
  Rats underwent an operation to induce RE, with or without rabeprazole treatment (1.0 and 10.0 mg/kg/day). Sham-operated rats served as a control. Fourteen days after the operation, esophagi were isolated from the rats and submitted to double-label confocal immunofluorescence microscopy, and biochemical analyses.
  
  
  RESULTS
  Immunofluorescence microscopy revealed that claudins-1, -3, and -4 were located on the surfaces of epithelial cells in the normal esophagus of the control group, although there were differences in the distribution patterns between claudin-3 and claudins-1 and -4 in the epithelial layer. However, in RE, the immunoreactivity of claudin-3 on the cell surface was decreased, and it appeared instead as a faint granular pattern within the epithelial cytoplasm. Claudin-3 expression in the entire esophageal epithelium was also decreased. The expression and location of claudins-1 and -4 in epithelial cells were basically unaffected in RE. Gastric acid-induced dissociation of claudin-3 elicited instability of the epithelial TJ complex, which was confirmed by sedimentation analysis using centrifugation in a sucrose density gradient. Rabeprazole (10.0 mg/kg/day) attenuated these alterations.
  
  
  CONCLUSIONS
  Our data indicate that the dispersion of claudin-3 from esophageal epithelial plasma membranes to cytoplasm and the resulting instability of the TJ complex could be one of the most specific and sensitive indicators for monitoring inflammatory and recovery processes in RE.
authors.affiliation: Department of Gastroenterology, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan. moguro@juntendo.ac.jp
authors.forename: Masako
authors.initials: M
authors.lastname: Oguro
authors.forename: Masato
authors.initials: M
authors.lastname: Koike
authors.forename: Takashi
authors.initials: T
authors.lastname: Ueno
authors.forename: Daisuke
authors.initials: D
authors.lastname: Asaoka
authors.forename: Hiroki
authors.initials: H
authors.lastname: Mori
authors.forename: Akihito
authors.initials: A
authors.lastname: Nagahara
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Uchiyama
authors.forename: Sumio
authors.initials: S
authors.lastname: Watanabe
mesh_terms: D053799:2-Pyridinylmethylsulfinylbenzimidazoles / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D062445:Claudin-1; D062465:Claudin-3; D062506:Claudin-4; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells / Q000378:metabolism; D004942:Esophagitis, Peptic / Q000175:diagnosis / Q000188:drug therapy / Q000473:pathology*; D007249:Inflammation / Q000175:diagnosis / Q000188:drug therapy / Q000473:pathology; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism*; D018613:Microscopy, Confocal; D008856:Microscopy, Fluorescence; D054328:Proton Pump Inhibitors / Q000008:administration & dosage / Q000494:pharmacology; D064750:Rabeprazole; D051381:Rats; D017208:Rats, Wistar; D019108:Tight Junctions / Q000378:metabolism*
chemical_list: D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D062445:Claudin-1; D062465:Claudin-3; D062506:Claudin-4; C568114:Cldn1 protein, rat; C568124:Cldn3 protein, rat; D008565:Membrane Proteins; D054328:Proton Pump Inhibitors; D064750:Rabeprazole